ArticleMolecular and cellular biochemistry2021
KLF9 regulates PRDX6 expression in hyperglycemia-aggravated bupivacaine neurotoxicity.
Article in Molecular and cellular biochemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Loss of Peroxiredoxin 6 Drives Age-Related Klf9/NF-Antioxidants (Basel, Switzerland) · 2026Article
- TXNIP-Deficiency and Prdx6 Delivery Inhibit Aging/Oxidative Stress-Driven TXNIP-Nlrp3 Inflammasome Activation and Mitigate Pyroptosis in Lens Epithelial Cells.Antioxidants (Basel, Switzerland) · 2026Article
- Peroxiredoxins in central nervous system: implications for chronic pain and anaesthetic-induced neurotoxicity management.Redox biology · 2025Review
- The Role of Nutraceuticals in Age-Related Ocular Diseases.Molecules (Basel, Switzerland) · 2025Review
- KLF9-Mediated Transcriptional Promotion of HMGB2 Accelerates Cardiomyocyte Apoptosis, Inflammation, and Ferroptosis in Myocardial Ischemia/Reperfusion Injury.Cardiovascular toxicology · 2025Article
- Peroxiredoxin 6 in Stress Orchestration and Disease Interplay.Antioxidants (Basel, Switzerland) · 2025Review
- Intermittent Fasting-Improved Glucose Homeostasis Is Not Entirely Dependent on Caloric Restriction in db/db Male Mice.Diabetes · 2024Article
- Review
- Prdx6 Regulates Nlrp3 Inflammasome Activation-Driven Inflammatory Response in Lens Epithelial Cells.International journal of molecular sciences · 2023Article
- Knockdown of Krüppel-Like Factor 9 Inhibits Aberrant Retinal Angiogenesis and Mitigates Proliferative Diabetic Retinopathy.Molecular biotechnology · 2023Article
- Anti-Oxidant and Pro-Oxidant Effects of Peroxiredoxin 6: A Potential Target in Respiratory Diseases.Cells · 2023Review
- Circular RNA_HIPK3-Targeting miR-93-5p Regulates KLF9 Expression Level to Control Acute Kidney Injury.Computational and mathematical methods in medicine · 2023Article
- Potential Properties of Natural Nutraceuticals and Antioxidants in Age-Related Eye Disorders.Life (Basel, Switzerland) · 2022Review
- Peroxiredoxins-The Underrated Actors during Virus-Induced Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundNeurotoxicity induced by local anesthetics (LAs) is potentially life threatening, especially for patients with underlying diseases like diabetes. The anesthetic bupivacaine (Bup) has been reported to induce neurotoxicity mediated by reactive oxygen species (ROS), which is aggravated by hyperglycemia. Krüppel-like factor 9 (KLF9), an axon growth-suppressing transcription factor, plays a key role in neuronal maturation and promotes oxidative stress. This study was designed to investigate whether and how KLF9 regulates ROS levels related to LA neurotoxicity under hyperglycemic conditions.
methodsKlf9/GFP ShRNA (LV Sh-Klf9) was used to achieve stable Klf9 knockdown in the SH-SY5Y cell line. KLF9-deficient and normal cells were cultured under normal or high-glucose (HG) culture conditions and then exposed to Bup. Cell viability, intracellular and mitochondrial ROS, and mitochondrial membrane potential (ΔΨm) were detected to examine the role of KLF9. Thereafter, KLF9-deficient and normal cells were pretreated with small-interfering RNA targeting peroxiredoxin 6 (siRNA-Prdx6) to determine if PRDX6 was the target protein in HG-aggravated Bup neurotoxicity.
resultsThe mRNA and protein levels of KLF9 were increased after Bup and hyperglycemia treatment. In addition, cell survival and mitochondrial function were significantly improved, and ROS production was decreased after Sh-Klf9 treatment compared with Sh-Ctrl. Furthermore, the expression of PRDX6 was suppressed by Bup in hyperglycemic cultures and was upregulated in the Sh-Klf9 group. Moreover, the protection provided by KLF9 deficiency for cell survival, the increase in ROS production in cells and mitochondria, and the disruption of mitochondrial function were abolished by Prdx6 knockdown.
conclusionsThe results of this study demonstrated that hyperglycemia aggravated Bup neurotoxicity by upregulating KLF9 expression, which repressed the antioxidant PRDX6 and led to mitochondrial dysfunction, ROS burst, and cell death. Understanding this mechanism may, thus, offer valuable insights for the prevention and treatment of neurotoxicity induced by LAs, especially in diabetic patients.
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